Polycystic kidney disease PKD2 gene and uses thereof

Abstract

The present invention provides a purified and isolated wild type PKD2 gene, as well as mutated forms of this gene. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the wild type PKD2 gene or the mutated PKD2 gene, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of ADPKD associated with the mutated PKD2 gene. The present invention also provides a method for diagnosing ADPKD caused by a mutated PKD2 gene, as well as a method for treating autosomal dominant polycystic kidney disease caused by a mutated PKD2 gene.

1. A method of detecting the absence of a mutation in the sequence of polycystic kidney disease type 2 (PKD2) gene in a human subject, comprising the steps of:
 (a) obtaining a polynucleotide sample containing the sequence of PKD2 gene from a human subject; 
 (b) comparing the polynucleotide sample to a reference human wild-type PKD2 sequence comprising SEQ ID NO:6; and 
 (c) determining the differences, if any, between the sequence of PKD2 gene in the polynucleotide sample and the reference wild-type PKD2 sequence comprising SEQ ID NO:6, wherein an absence of differences between the sequence of PKD2 gene in the polynucleotide sample and the reference wild-type PKD2 sequence comprising SEQ ID NO:6 is indicative of the absence of a mutation in the sequence of PKD2 gene in a human subject. 
 
     
     
       2. The method of  claim 1 , wherein the subject is an embryo, fetus, newborn, infant, or adult. 
     
     
       3. The method of  claim 1 , wherein the polynucleotide sample is DNA or RNA. 
     
     
       4. A method of detecting the absence of a mutation in the sequence of polycystic kidney disease type 2 (PKD2) gene (SEQ ID NO:6) in a human subject, comprising the steps of:
 (a) obtaining a polynucleotide sample containing the sequence of PKD2 gene from a human subject, wherein SEQ ID NO:6 is human wild-type PKD2 gene sequence; and 
 (b) performing sequence analysis of the polynucleotide sample to detect the absence of a mutation in the sequence of PKD2 gene (SEQ ID NO:6) of the human subject, wherein the mutation comprises a deletion, insertion, point, or rearrangement mutation. 
 
     
     
       5. The method of  claim 4 , wherein the subject is an embryo, fetus, newborn, infant, or adult. 
     
     
       6. The method of  claim 4 , wherein the polynucleotide sample is DNA or RNA. 
     
     
       7. A method of detecting the presence or absence of a mutation in the nucleotide sequence of polycystic kidney disease type 2 (PKD2) gene in a human subject comprising the steps of:
 (a) obtaining a polynucleotide sample containing the sequence of polycystic kidney disease type 2 (PKD2) gene from a human subject; 
 (b) comparing the polynucleotide sample to a nucleotide sequence comprising SEQ ID NO:6, wherein SEQ ID NO:6 is human wild-type PKD2 gene sequence; and 
 (c) determining the differences, if any, between the sequence of PKD2 gene in the polynucleotide sample and the nucleotide sequence comprising SEQ ID NO:6, wherein the human wild-type PKD2 sequence is SEQ ID NO:6, and thereby detecting the presence or absence of a mutation in the nucleotide sequence of PKD2 gene in a human subject. 
 
     
     
       8. The method of  claim 7 , wherein the subject is an embryo, fetus, newborn, infant, or adult. 
     
     
       9. The method of  claim 7 , wherein the polynucleotide sample is DNA or RNA. 
     
     
       10. A method of detecting the presence or absence of a mutation in the sequence of polycystic kidney disease type 2 (PKD2) gene in a human subject, comprising the steps of:
 (a) obtaining a polynucleotide sample containing the sequence of PKD2 gene from between genetic markers /AFMa059xc9 and AICA1 on chromosome 4 from a human subject, wherein genetic markers AFMa059xc9 and AICA1 flank the PKD2 gene; 
 (b) comparing the polynucleotide sample to a reference human wild-type PKD2 sequence comprising SEQ ID NO:6; and 
 (c) determining the differences, if any, between the sequence of PKD2 gene in the polynucleotide sample and the reference wild-type PKD2 sequence comprising SEQ ID NO:6, wherein the differences are mutations of PKD2 gene which comprise one or more deletion, insertion, point, or rearrangement mutations; and thereby detecting the presence or absence of a mutation in the sequence of PKD2 gene in a human subject. 
 
     
     
       11. The method of  claim 10 , wherein the subject is an embryo, fetus, newborn, infant, or adult. 
     
     
       12. The method of  claim 10 , wherein the polynucleotide sample is DNA or RNA.